TY - JOUR
T1 - A bi-allelic loss-of-function SARS1 variant in children with neurodevelopmental delay, deafness, cardiomyopathy, and decompensation during fever
AU - Ravel, Jean-Marie
AU - Dreumont, Natacha
AU - Mosca, Pauline
AU - Smith, Desiree E. C.
AU - Mendes, Marisa I.
AU - Wiedemann, Arnaud
AU - Coelho, David
AU - Schmitt, Emmanuelle
AU - Rivière, Jean-Baptiste
AU - Tran Mau-Them, Frédéric
AU - Thevenon, Julien
AU - Kuentz, Paul
AU - Polivka, Marc
AU - Fuchs, Sabine A.
AU - Kok, Gautam
AU - Thauvin-Robinet, Christel
AU - Guéant, Jean-Louis
AU - Salomons, Gajja S.
AU - Faivre, Laurence
AU - Feillet, François
N1 - Funding Information: The authors thank the family for participating in this study. We thank the University of Burgundy Centre de Calcul (CCuB) for technical support and informatics platform management. We thank Dr. Xiang-Lei Yang (Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA) for kindly providing the pFLAG-CMV plasmid containing SARS1 cDNA. This study was supported by Dijon University Hospital grants, the ISITE-BFC (PIA ANR), and the European Union through the FEDER programs. Several authors of this publication are members of the European Reference Network for Developmental Anomalies and Intellectual Disability (ERN-ITHACA). Funding Information: The authors thank the family for participating in this study. We thank the University of Burgundy Centre de Calcul (CCuB) for technical support and informatics platform management. We thank Dr. Xiang‐Lei Yang (Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA) for kindly providing the pFLAG‐CMV plasmid containing cDNA. This study was supported by Dijon University Hospital grants, the ISITE‐BFC (PIA ANR), and the European Union through the FEDER programs. Several authors of this publication are members of the European Reference Network for Developmental Anomalies and Intellectual Disability (ERN‐ITHACA). SARS1 Publisher Copyright: © 2021 Wiley Periodicals LLC
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Aminoacyl-tRNA synthetases (aaRS) are ubiquitously expressed enzymes responsible for ligating amino acids to their cognate tRNA molecules through an aminoacylation reaction. The resulting aminoacyl-tRNA is delivered to ribosome elongation factors to participate in protein synthesis. Seryl-tRNA synthetase (SARS1) is one of the cytosolic aaRSs and catalyzes serine attachment to tRNASer. SARS1 deficiency has already been associated with moderate intellectual disability, ataxia, muscle weakness, and seizure in one family. We describe here a new clinical presentation including developmental delay, central deafness, cardiomyopathy, and metabolic decompensation during fever leading to death, in a consanguineous Turkish family, with biallelic variants (c.638G>T, p.(Arg213Leu)) in SARS1. This missense variant was shown to lead to protein instability, resulting in reduced protein level and enzymatic activity. Our results describe a new clinical entity and expand the clinical and mutational spectrum of SARS1 and aaRS deficiencies.
AB - Aminoacyl-tRNA synthetases (aaRS) are ubiquitously expressed enzymes responsible for ligating amino acids to their cognate tRNA molecules through an aminoacylation reaction. The resulting aminoacyl-tRNA is delivered to ribosome elongation factors to participate in protein synthesis. Seryl-tRNA synthetase (SARS1) is one of the cytosolic aaRSs and catalyzes serine attachment to tRNASer. SARS1 deficiency has already been associated with moderate intellectual disability, ataxia, muscle weakness, and seizure in one family. We describe here a new clinical presentation including developmental delay, central deafness, cardiomyopathy, and metabolic decompensation during fever leading to death, in a consanguineous Turkish family, with biallelic variants (c.638G>T, p.(Arg213Leu)) in SARS1. This missense variant was shown to lead to protein instability, resulting in reduced protein level and enzymatic activity. Our results describe a new clinical entity and expand the clinical and mutational spectrum of SARS1 and aaRS deficiencies.
KW - SARS1
KW - aminoacyl-tRNA synthetase
KW - aminoacylation
KW - brain
KW - deafness
KW - death
KW - intellectual disability
KW - tRNA
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85116501009&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/34570399
UR - http://www.scopus.com/inward/record.url?scp=85116501009&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/humu.24285
DO - https://doi.org/10.1002/humu.24285
M3 - Article
C2 - 34570399
SN - 1059-7794
VL - 42
SP - 1576
EP - 1583
JO - Human mutation
JF - Human mutation
IS - 12
ER -